INTRODUCTION:

Despite significant advancements in drug delivery technology, oral route is most preferred route of administration for variousactive ingredients due to improved patient compliance, ease of administration, flexibility in design of formulation etc. ^[1-2].Orally administeredconventional dosage forms (tablets, capsules etc)do not have proper control over drug release and leads to high fluctuations in plasma drug concentrationsin comparison with controlleddosage forms which have ability to release active ingredient in predetermined and controlled manner with no fluctuation in plasma drug concentrations ^[3-4]. Controlled release drug delivery systemsare widely employed due to various advantages (enhanced therapeutic action with improved bioavailability)over other conventional dosage forms.

Many constraints are associated with developmental process of conventional controlled release dosage forms such as these systems cannot retain and locate the dosage form within the specific area of the gastrointestinal tract (GIT), variations in gastric emptying time and motility pattern of GIT^[2,5]. Gastric emptying time of formulations show high variation and can lasts from few minutes to 12 h which depends upon the design and development process of pharmaceutical formulations and physiological state of subject. Because most of the therapeutic agents preferably absorbed in upper part of small intestine and variation in gastric emptying time may leads to unpredictable time to achieve peak plasma levels^[6]. In addition, short gastric emptying times of formulations which normally occur between 2 to 3 h through the major absorption regionleads to inappropriatedrug release from the drug delivery systemand reduced therapeutic efficacy of the orally administered dosage forms. Therefore, it is necessary to control over placement of a dosage form in a particular area of the GITprovide various advantages, particularly for drugs which have stability problem or low absorption window in the GI tract. Drug absorption property of low absorption window drugs is greatly affected by overall contact of dosage form with the absorbing surface of the membranes.Gastric retention abilities of orally administered controlled release drug delivery systems can be improved by above considerations ^[7-10].

Gastroretentive Drug Delivery Systems:

Gastroretentive dosage forms are oral dosage forms with gastric retention capabilities in the GI tract(GRDDS). These systems are highly suitable for drugs that posse’s absorption window constraints, by improving gastric residenceswith controlled release abilities continuously release active ingredientfrom the dosage form over prolonged period of time and enhances oral bioavailability before it reaches its absorption site^[11-14].

Gastroretentive Technologies:

Different development approaches have been frequently utilized in pharmaceutical industry with improved gastric retention capabilities in the GIT such as floating drug delivery systems, swelling and expanding systems, bioadhesive drug delivery systems, and other delayed gastric emptying devices as shown in Figure 1. Based on the principles ofgastric residence abilities gastroretentive dosage forms have been classified which are briefly described in following text.

Fig. 1 Gastroretentive technologies

High density systems:

These systems can withstand peristaltic movements of the stomach by retaining active drug molecule in the rugae of stomach and. Density of the gastric content is 1.004 gm/cm³ which is close to water. These dosage forms have good ability to withstand peristaltic movements of the stomach wall because these are pellets of high density and if patient is in upright posture, then these pellets sink to the bottom of the stomach due to high density and entrapped in the folds of the antrum. Density of gastric content near about 2.5 gm/cm³is sufficiently effective to prolong the gastric residence time. An effective development approach for preparation of these formulations is mixing of drug coated heavy core with barium sulphate, iron powder, zinc oxide and titanium oxide etc. act as inert materials. After this step these materials increases the density of the dosage form upto 1.5- 2.4 gm/cm³ which is close to density of gastric content^[15-19].

Expanding systems:

If size of the dosage form is larger than size of the pyloric sphincter of the stomach, this type of dosage form issuitable to resistgastric transit property of the stomach. With consideration of large size regarding gastric transit but size of dosage form must be small enough so that it can be easily swallowed by patient without causing any type ofobstruction in stomach when used single or in combination. For utilization of expanding approach for gastric retention there is requirement of three main parameters (First requirement is small size for oral ingestion of dosage form enables evacuation with good release characteristics ^[20-21]. There are mainly two approaches which can be used to design expanding systems given in the following text.

Swellable systems and Unfoldable systems:

Swelling systems are type of gastroretentive systems which after contact with gastric content swells to large size and pylorus sphincter prevents the passage of swelled dosage form due to large size ^[22]. These dosage forms are retained in the stomach for prolonged period of time due to swelling of dosage form.Sometimes these gastric retentive dosage forms are known as plug typedosage formsbecause their tendency to lodged at the pyloric sphincter ^[23]. Utilization of polymeric materials which have swelling property in presence of gastric fluids increases the size of dosage form blocks the entry form pyloric sphincter.Control over swelling rate and polymer erosion is important factor in maintenance of maximum therapeutic effects and minimization ofunwanted side effects. Swelling behaviours of theses formulations are due to osmotic absorption of water and size of the dosage form is optimum for easy swallowing and makes them effectively suitable for gastric retention ^[24-30].Unfoldable type of gastric retentive dosage forms are generally prepared by using biodegradable polymeric materials. These systems occurs in different geometric arrangements such as tetrahedron, ring or planner membrane (4 – label disc or 4 – limbed cross form)made up of bioerodible polymers packed within a capsule which have extendableability in the stomach and improved gastric retention.

Superporous hydrogel, systems:

Superporous hydrogels are swellable type of drug delivery systems; differ from the conventional types to dosage forms. Conventional hydrogels have slow water absorption process with pore size ranges from 10 nm to 10 μm. To reach an equilibrium state it may take several hours during which early evacuation of the drug delivery system may occurs. Superporous hydrogels (pore size >100 μm) swells within a minute to attain equilibrium size average, due to rapid water uptake by capillary wetting through numerous interconnected open pores. Moreover, they swell to a large size (swelling ratio 100 or more) and are intended to have sufficient mechanical strength to withstand pressure by gastric contraction. This is achieved by co-formulation of a hydrophilic particulate material, Ac-Di-Sol (croscarmellose sodium) ^[31-33].

Bioadhesive drug delivery systems:

Bioadhesive systems are gastroretentive type dosage forms effectively increase site specific absorption of drugs after oral administration. Bioadhesive polymeric materials are used to achieve adhesion of dosage form to the epithelial surface in the gastric region and prolonged gastric residence time. Dosage forms can show bioadhesive properties by different mechanisms which are based uponsimple process in which dosage form adhere to the surface of mucous membrane. Frequently used polymeric materials for bioadhesive purpose are chitosan, cholestyramine, sodium alginate, poly acrylic acid, hydroxypropyl methyl cellulose, sucralfate, tragacanth, dextrin, and polylactic acids etc. But there are some constraints are associated with these polymeric materials because some of these materials effectively produced bioadhesive properties but difficult to maintain this adhesiveness due to rapid turnover rate of mucus in gastric tract ^[34-35].

Floating drug delivery systems:

Floating systems are one of the most effective approaches used for gastric retention in order to achieve better drug bioavailability with prolonged gastric residence times among all other gastroretentive type of dosage systems ^[7]. Floating systems are suitable drug delivery systems for drugs which have absorption window constraints with improved results of absorption window problems window in the stomach or in the upper small intestine ^[11]. These systems have ability to retain in the stomach for prolonged period of time without affecting the gastric emptying rates because of their low bulk density than gastric fluids.Because of their effective buoyancy characteristics they show good gastric retention where the dosage formrelease drug slowly in predetermined and controlled manner and after complete release of drug, the residual system is emptied from the stomach ^[36].

In order to design successful floating dosage forms, three major conditions should be met: (a) these systems must have 1.004 – 1.01 gm/cm³ specific gravity which is less than gastric contents. (b) Drug release from the dosage form should be slow to act as a reservoir type system (c) floating systems must form a cohesive gel like barrier^[37]. Hydrodynamically balanced systems are floating controlled release dosages forms made up of hydrophilic polymeric matrices. When these systems come in contact with gastric fluids, polymer become hydrated and forms a gel like barrier at the surface and remain buoyant in the stomach due to their low bulk density and prolongs the gastric residence time of the systems.Floating systems have ability to retain in gastric content and with buoyancy of about 3 to 4 h without any variation in gastric emptying rate. Hydroxy propyl methyl among cellulose ether polymers is most preferred hydrocolloidal material recommended for floating controlled release dosage forms ^[38-40]. Table 1 shows some commercially available gastroretentive formulations.

Table 1: Commercial gastro retentive formulations

S.No.	Name	Type and Drug	Remarks
1.	MadoparHBS^a	Floating capsule, Levodopa and Benserazide	Floating Capsules
2.	Valrelease	Floating capsule, Diazepam	Floating Capsules
3.	Topalkan	Floating antacid, Aluminium and Magnesium mixture	Effervescent floating liquid alginate preparation
4.	Conviron	Ferrous sulphate	Colloidal gel forming FDDS
5.	Cifran OD	Ciprofloxacin (1gm)	Gas generating floating form

CONCLUSION:

By prolongation of the gastric retention timeof the drugs these systems offers various advantages such as predetermined and rate controlledrelease of the drug with optimum availability of drug in an absorbable form at specific regions of GIT.Various low absorption drugs can be easily formulated in controlled release systems by improved gastric retention properties. It is expected that the gastroretentive approach can be frequently used for administrationof various active agents with novel biodegradable polymeric materials and provides more effective therapeutic results. Moreover, new advancements in drug delivery technology will definitely provide real prospects for development of novel and better means in the fabrication of these promising drug delivery systems.

CONFLICT OF INTEREST:

Authors do not have any conflict of interest.

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Received on 12.01.2018 Modified on 11.03.2018

Research J. Pharm. and Tech 2018; 11(5): 2157-2160.

DOI: 10.5958/0974-360X.2018.00398.0